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Hines posted an update 1 year ago
Weights of methylene chloride predominated the mixture index in all lag periods. Our study suggests an increased risk of ALS in men exposed to multiple solvents, with the greatest influence being from methylene chloride. These findings highlight the need to utilize mixtures analysis when considering co-occurring exposures.Schizophrenia (SCZ) and bipolar disorder (BD) are severe psychiatric disorders that share many genetic risk factors. This study aimed to investigate the association of phosphoinositide-3-kinase regulatory subunit1 (PIK3R1) gene rs3756668 and rs3730089 polymorphisms with SCZ and BD risks and determine the expression levels of PIK3R1. A total of 548 SCZ cases, 512 BD cases, and 598 healthy controls were included in this study. Single nucleotide polymorphisms (SNPs) were genotyped using the Sequenom MassARRAY platform, and quantitative reverse transcription polymerase chain reaction was conducted to examine the mRNA expression of PIK3R1. The genotypic distribution of rs3756668 in the BD group was significantly different from that in the healthy controls (P = 0.038). After adjustment for gender and age was made, rs3730089 was significantly associated with the risk of SCZ [AA/(AG + GG) OR = 2.25, Padj = 0.040; AA/GG OR = 2.27, Padj = 0.038]. The SNP rs3756668 was associated with the susceptibility of BD (AA+GG/AG OR = 0.73, P = 0.011) and the association remained after adjusting for gender and age. The mRNA level of PIK3R1 was significantly upregulated in patients with BD compared with that in the control group (P less then 0.001). In terms of the diagnostic value of PIK3R1 for BD, the receiver operating characteristic curve analysis showed an area under the curve of 0.809 with 74.0% sensitivity and 73.9% specificity. PIK3R1 may be the shared susceptibility gene of SCZ and BD and may be a potential diagnostic biomarker for BD.The chive maggot, Bradysia odoriphaga (Yang and Zhang) is an economically important insect pest, affecting many key vegetables, including Chinese chive, especially in northern China. Chlorfenapyr, a halogenated pyrrole insecticide that interferes with mitochondrial oxidative phosphorylation is widely used against B. odoriphaga. In this study, we evaluated selection-induced resistance to chlorfenapyr and fitness costs in B. Pomalidomide odoriphaga. The results showed that B. odoriphaga developed 43.32-fold resistance after continuous exposure to chlorfenapyr for over 10 consecutive generations. The life-history traits of chlorfenapyr-resistant and susceptible strains were compared using age-stage, two-sex life table approach. No significant effects were observed on the longevity and pre-adult period. However, reduction in the total pre-oviposition period (TPOP) and fecundity (eggs/female) were observed in the resistant strain. Moreover, the demographic parameters such as intrinsic rate of increase (r), net reproductive rate (R0) and finite rate of increase (λ) were also decreased significantly in the resistant strain compared to the susceptible strain. These results showed the potential of B. odoriphaga to develop resistance against chlorfenapyr under continuous selection pressure. Furthermore, there was a fitness cost linked with chlorfenapyr resistance in B. odoriphaga. We conclude that a better knowlegde on the trade-off at play between resistance degree and fitness cost could be crucial for developing further management of B. odoriphaga in China.The advent of computational methods for efficient prediction of the druglikeness of small molecules and their ever-burgeoning applications in the fields of medicinal chemistry and drug industries have been a profound scientific development, since only a few amounts of the small molecule libraries were identified as approvable drugs. In this study, a deep belief network was utilized to construct a druglikeness classification model. For this purpose, small molecules and approved drugs from the ZINC database were selected for the unsupervised pre-training step and supervised training step. Various binary fingerprints such as Macc 166 bit, PubChem 881 bit, and Morgan 2048 bit as data features were investigated. The report revealed that using an unsupervised pre-training phase can lead to a good performance model and generalizability capability. Accuracy, precision, and recall of the model for Macc features were 97%, 96%, and 99%, respectively. For more consideration about the generalizability of the model, the external data by expression and investigational drugs in drug banks as drug data and randomly selected data from the ZINC database as non-drug were created. The results confirmed the good performance and generalizability capability of the model. Also, the outcomes depicted that a large proportion of misclassified non-drug small molecules ascertain the bioavailability conditions and could be investigated as a drug in the future. Furthermore, our model attempted to tap potential opportunities as a drug filter in drug discovery.Although the literature is growing regarding large-scale, system-wide implementation programs, the broader political and social contexts, including race and ethnicity, are frequently ignored. Using the Policy Ecology of Implementation framework (Raghavan et al., Implement Sci 326, 2008), Minnesota’s CEMIG is examined to investigate the role of social and political contexts in the implementation process and the barriers they create. Data from 22 interview transcripts from DHS administrators, agency grant managers, university educators, advocacy group representatives, and mental health board members, along with more than 1000 grant documents were qualitatively analyzed using content analysis to reveal three themes concerning how the participants experienced program implementation invisibility, isolation, and inequity. Findings demonstrate the participants perceived that the grant program perpetuated inequities by neglecting to promote the program, advocate for clinicians of color, and coordinate isolated policy ecology systems. Strategies for future large-scale, system-wide mental health program implementation are provided.